• Defects early in the pathway produce precursors which are neurotoxic and produce acute porphyrias. They show #autosomalDominant inheritance.
• More common are defects later on in the pathway cause accumulation of porphyrins leading to chronic porphyria; This is known as porphyria cutanea tarda.

[!TIP] Patient (esp. Female) with abdominal pain + neuropsychiatric features -> need to consider acute porphyria.

• Clinical features: Abdominal pain, neuropsychiatric features, seizures and fever.

• Can be precipitated by anaesthetic drugs and luteal phase of the menstrual cycle.

• Anaesthesia for suspected acute abdomen can be catastrophic.

• The defective enzyme in acute intermittent porphyria is porphobilinogen deaminase.

• The defect is in uroporphyrinogen decarboxylase.

• 80% of cases are acquired / sporadic; 20% are inherited.

• Uroporphyrinogen decarboxylase converts uroporphyrinogen III into coproporphyrinogen III.

• Presents with photosensitive blistering rash.

• Hypertrichosis and hyperpigmentation may be present.

• Liver disease is a common comorbidity:

  • Either caused by excessive hepatic porphyrins OR
  • liver disease due to hepatitic C / alcohol triggering porphyria.

• Triggers for attacks are caused by increased hepatic iron load but also alcohol, smoking, estrogens, hepatitis C or HIV.

• Phlebotomy - used to decrease the iron load.

• Hydroxycholorquine - increase the excretion of porphyrins.

• Cutaneous T cell lymphoma - usually limited to the skin. Looks like tinea versicolor.
• benign course

Sezary syndrome

• Sezary syndrome is an erythrodermic cutaneous T-cell lymphoma with the leukemic component.

    1. Overnight 1mg dexamethasone suppression test

• Primary adrenal insufficiency is also called Addison's disease
• Features: ⬇Na, ⬆K, ⬇pH
• Diagnosis
  • Screening: morning cortisol level.
  • confirmatory: Short synacthen test. (plasma cortisol is measure before and 30 minutes after administration of IM 250ug of Synacthen)
  • Other investigations (not related to Addison's disease):
    • 24 hour urinary free cortisol is used to check for cushing's syndrome; not Addison's.

Psoriatic arthritis is associated with HLA-B27.

Imaging

Psoriatic arthritis Vs. Rheumatoid arthritis

Differentiation is clinically important because prognosis and management are different.

Summary of enzymes involved

HMG-CoA reductase: Rate limiting enzyme in cholesterol sythesis : found in the liver and ? other tissues
LCAT : the enzyme synthesized by the liver and attached to HDL which exterifies cholesterol so that it becomes trapped inside HDL. Required for reverse transport of cholesterol.
LPL: lipoprotein lipase: the enzyme found on tissues which removes lipids from VLDL and it's derivatives, increasing their density.
If there is acidosis (pH < 7.2 or HCO3 < 15) or high ketonemia, manage as DKA.
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+ it is **non pruritic**, starts on the abdomen and **spreads *outwards***. (Spares palms and soles) 

Trombiculid mite = 'harvest' mite

Endemic typhus serves as the prototype for pathogenesis:
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[!INFO] DCT physiology

• Reabsorbs 5% of the filtered potassium.
• Contains thiazide sensitive Na/Cl co-transporter.
• Also contains TRPV-5 for calcium reabsorption.

Inheritance: #autosomal-Recessive

• Thiazides and Gitelman affect the same transporter (NCCT)

These changes (except the lack of hyponatremia) are very similar to changes caused by chronic thiazide use.

8. Endocrine: reduced testosterone (due to Leydig cell dysfunction) [Source](https://emedicine.medscape.com/article/120858-overview)

• Activated charcoal isn't effective
• Long term, may need liver transplantation.
• Antidotes: Ethanol and fomepizole.
  | Dermatologic condition | Associated |
  | ---- | ---- |
  | Hyperkeratotic and proliferative dermatoses | - |
  | [[2022 General Medicine Paper-May#Acanthosis nigricans]] | |
  | Florid cutaneous papillomatosis (rapid eruption of warts) | Stomach cancer |
  | Sign of Leser-Trelat (rapid appearance of seborrheic keratoses) | Gastrointestinal adenocarcinoma AND many others |
  | Tripe palm (velvety thickening of palmar skin) | Gastric or lung cancer |
  | Icthyosis | Hodgkin's lymphoma |
  | Palmoplantar keratoderma | Associated with SQC of oesophagus = Howel-Evans Xn |
  | Bazex Xn: psoriatic like plaques on fingers and toes (acrokeratosis paraneoplastica | SQC of aerodigestive tract |
  | Inflammatory dermatoses - erythematous or violaceous skin eruptions | |
  | Sweet syndnrome (dermal,non vasculitic neutrophil infiltration with fever + neutrophilia) | Acute myeloid leukemia, lymphoma |
  | Dermatomyositis | Ovarian, breast, cervical,uterine + others |
  | Erythroderma (usually caused by psoriasis or atopic dermatitis) | Cutaneous T cell lymphoma |
  | Erythroderma gyratum repens | Bronchogenic carcinoma |
  | Pancreatic panniculitis | Pancreatic cancer |
  | paraneoplastic pemphigus (PAMS) | Non-hodgkin lymphoma, CLL |
  | Mucous Membrane pemphigoid | Unspecified but associated with malignancy |
  | - | |
  | Hyperpigmentation | |
  | Hyperpigmentation in ectopic ACTH poduction (ectopic cushing's syndrome) | Small cell lung CA |
  | ( POMC produced by the tumour is a precursor of ACTH and MSH ) | |
  | Generalized dermal melanosis | Extensive metastatic melanoma |
  | Skin manifestations of amyloidosis [[2022-November#Amyloidosis]] | plasma cell dyscrasias such as multiple myeloma, and less frequently, Waldenström macroglobulinemia |

• reduce alcohol - specially beer, avoid high fructose foods (like soft drinks)
• Reduce total calorie and cholesterol intake.
• Avoid red meat, spinach.
• First few episodes of gout are managed symptomatically as above. (new guidelines recommend ULT from first episode)

• [[Hormone Physiology#Adrenaline synthesis]]

Interface hepatitis is seen, just like autoimmune hepatitis.
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🔖Extrahepatic manifestations of hepatitis B

• Serum sickness like syndrome
• Oral lichen planus
• Papular acrodermatitis
• 
  • Which is also called ?Gianotti Crosti syndrome
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• and lincosamide - clindamycin.

Symptoms : N/V, headache,
motor effects: nystagmus, tremor, cerebellar ataxia.

Phenytoin side effects

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• TCAs have been overall surpassed by SSRIs probably because of their toxicity
• Mechanism : Inhibition of presynaptic neurotransmitter reuptake
• Toxic effects:
  • Cardiac conduction abnormalities ( conduction defects due to increased refractory period, prolonged repolarization) occur during tricyclic antidepressant (TCA) poisoning because TCAs inhibit the fast sodium channels in the His-Purkinje system and myocardium -> slowing down of conduction; Most suggestive feature: widened QRS, prolongation of PR and QT also possible)
  • Metabolic acidosis occurs in severe poisoning. Acidosis augments drug toxicity.
  • 
• Hypotension From peripheral alpha 1 blockade as well as cardiac effects
• Antimuscarinic effects - tachycardia, hyperthermia, flushing, dilated pupils
• CNS effects: sedation, but may also include confusion, delirium, or hallucinations
• increases pH (goal 7.5) - favors unionised form of the drug -> less affinity to bind to sodium channels.
• Benzodiazepines for agitation
• Saline for hypotension
• Despite prominent anticholinergic toxicity in some, physostigmine is contraindicated (incr. risk of arrest)

Antipsychotic drugs

Causes of hyperprolactinaemia

#2023GM-NOV/Q30
Pathological causes

• Lactotroph adenoma
• Decreased dopaminergic inhibition
• Other hypothalaic or pituitary disorders

Drugs:

• Antipsychotics : commonest drugs causing hyperprolactinaemia (eg. Haloperidol, risperidone)
  • Newer drugs: occurs with amisulpride.
  • Does not occur with clozapine.
• SSRI's do NOT cause hyperprolactinaemia.
• Other drugs:
  • Metoclopramide (centrally acting dopamine and serotonin angatonist) and domperidone (peripherally acting dopamine antagonist) can cause hyperprolactinaemia .
    • Domperidone does not cross the blood brain barrier.
    • Methyldopa inhibits dopamine synthesis.